PhD Student
Transformation of Advanced
Medicines Manufacture (TRANS-AM)
Gene
therapies are a type of advanced medicine that represent exciting possibilities
to treat and potentially cure many life-altering and life-threatening diseases.
They also represent a huge growth area with several hundred currently in
various stages of development. Many of these are based on using recombinant
Adeno-associated virus (rAAV) as a delivery vector. If even a small portion of
them reach the market, current manufacturing and characterisation technologies
in the industry will struggle to deliver them economically and safely for
patients.
This
research program aims to provide innovative solutions to help overcome the
manufacturing challenges associated with producing rAAV and brings together
experts from two leading Irish institutions, NIBRT and UCD, and APC-VLE Ltd. (https://approcess.com/services/cell-and-gene-therapies)
- a leading Irish industrial partner - in an exciting 5-year collaborative
program.
We
are currently seeking applicants for three PhD projects as listed below. The
successful candidates will be based in either NIBRT or UCD and will also spend
some time on placements in the industrial partner.
We are seeking
ambitious, inquisitive and innovative individuals to join our multidisciplinary
research team. As part of a dynamic and collaborative environment, you will
contribute to breakthrough work that supports the scalable, efficient, and
high-quality production of viral vectors—laying the foundation for
next-generation treatments for genetic diseases. If you're excited by the
intersection of biotechnology, process development, and therapeutic innovation,
we’d love to hear from you.
The National Institute for Bioprocessing Research and
Training (‘NIBRT’) is a global centre of excellence, headquartered in
Dublin that provides training and research solutions to the global
biopharmaceutical manufacturing sector. NIBRT arose from an innovative
collaboration between University College Dublin, Trinity College Dublin, Dublin
City University and the Institute of Technology, Sligo, with core funding from
the Government of Ireland through Ireland’s inward investment agency, IDA
Ireland. NIBRT’s 8,300 m² facility has over 100 employees currently and houses
fully operational pilot plants for biologics manufacturing training to industry
and education, multiple research laboratories focused on biopharmaceuticals
manufacturing research and a dedicated facility focused on the early-stage
development of biologics and advanced therapy products. The facilities and
infrastructure are world-leading and provide a vibrant environment for delivery
of excellent science and translation research and opportunities for career
growth, development and progression.
UNIVERSITY COLLEGE
DUBLIN (UCD) is one of Europe’s leading
research-intensive universities where undergraduate education, postgraduate
masters and PhD training, research, innovation and community engagement form a
dynamic continuum of activity. The University was established in 1854 by John
Henry Newman whose classic work The Idea of a University is one of the most
enduring texts on the value of higher education and a source of inspiration for
UCD’s current educational philosophy.
Today UCD
is Ireland’s largest university with almost 25,000 students. It is the most
popular destination for Irish school-leavers and actively promotes university
life as a journey of academic and personal discovery through its highly
innovative and flexible UCD Horizons undergraduate curriculum. UCD is Ireland’s
leader in postgraduate education with almost 7,000 postgraduate students,
representing approximately 28% of the UCD student population, and almost 2,000
PhD students. Over 50% of UCD undergraduates progress to postgraduate studies.
Project 1: CRISPR library screening
to identify endogenous HEK293 genes that impact AAV production
Supervisors:
Prof. Niall Barron & Assoc. Prof. Colin Clarke
About the project:
A strategy that has proven very successful
in identifying the genetic basis of various
cellular phenotypes, including diseases
such as cancer, cellular behaviour in bioreactors and identifying viral
restriction factors, is the use of CRISPR library screens. These can be either
to knockout the genes expressed in a cell or to activate the expression of
silent genes. The advantage is that it is relatively unbiased and has the
potential to target every gene in the genome.
Aims and Objectives: In this project we will use this strategy in order to screen a
suspension-adapted HEK293 cell line for genes that contribute to or inhibit the
production of AAV gene therapy vectors. We will use a human CRISPR/guide RNA
library to create a HEK293 cell population within which every gene has been
targeted for deletion. We will select a sub-population
of cells with the highest and lowest level of AAV production and this
population of cells will be sequenced to identify which guide RNAs are
enriched, thereby identifying their target genes. The most impactful genes will
be validated by knocking out in parental HEK293 cells and then testing AAV
production yield after triple transfection.
Candidate profile: Applicants should hold or expect to receive an upper 2.1 or 1.1
degree in a relevant discipline. A cell biology/molecular biology background would
be ideal. Training will be provided in advanced methods and approaches in cell
and molecular biology required for successful completion of the programme. The
ability to work as part of a team, a strong interest in applied research,
motivation to learn new skills as well as excellent written and oral skills are
essential.
Example publications from the Lab:
·
Production of an Oncolytic
Adeno-Associated Virus Containing the Pro-Apoptotic TRAIL Gene Can Be Improved
by shRNA Interference. 2025 Int J Mol Sci. Link
·
Multiplex genome editing eliminates
lactate production without impacting growth rate in mammalian cells. 2025 Nat
Metab. Link
·
Detection of host cell
microprotein impurities in antibody drug products. 2024 Nature
Communications. Link
· A Direct Comparison of rAAV5 Variants Derived from the Baculovirus
Expression System Using LC-MS Workflows Demonstrates Key Differences in Overall
Production Yield, Product Quality and Vector Efficiency. 2024 Int J Mol Sci.
Link
How to apply:
Project 1 applicants should email: a cover
letter
(including your motivation statement outlining why you wish to do a PhD and why you are suited to this project), a CV,
and contact details for your academic
referees to careers@nibrt.ie.
Informal enquiries to:
Funding:
Annual stipend of €25,000 plus fees for 4
years.
Project 2: Improving rAAV safety
through glycoengineering
Supervisors: Dr Ioscani Jiménez del Val
Recombinant
adeno-associated viruses (rAAVs) are the leading vectors for gene therapy, with
eight rAAV-based therapies with regulatory approval (EMA and/or FDA) and over
250 rAAV-based therapies undergoing clinical trials. Despite their success in
treating life-threatening illnesses, the rAAV doses required to achieve
therapeutic benefit often lead to immune responses that reduce efficacy and, in
extreme cases, may lead to patient death.
The capsid proteins
of rAAVs are decorated with complex carbohydrates (glycans), the composition of
which may drive dangerous immune responses in patients. For example, the immune
system is known to target high mannose carbohydrates present on the envelope of
several pathogenic viruses. Recent research has found that the majority of rAAV
glycans are high-mannose, further suggesting that glycans play an important
role in rAAV safety.
This project aims to
engineer rAAV carbohydrates, converting pathogenic high-mannose structures into
non-immunogenic forms. Initially, the project will remodel rAAV glycans using
in vitro methods. Once the immunological benefit of rAAV glycoengineering is
established, the project will continue with genetically engineering HEK293
cells, the most widely used host for rAAV production, to yield gene therapy
vectors with non-immunogenic glycans.
This exciting project
offers a mix of enzyme catalysis, molecular biology, cell culture, in vitro
assay development, and data analytics. We are looking for candidates that are
interested in these areas and who wish to deploy genetic engineering strategies
to advance the safety and efficacy of next-generation biological medicines.
Candidate profile: Applicants should hold or expect to receive an upper 2.1 or 1.1
degree in a relevant discipline, such as Biochemistry, Biotechnology, Cell
Biology, or Biochemical Engineering. Experience in mammalian cell culture and
molecular biology techniques are preferred. Training will be provided on the
methods required for successful project completion. Teamwork, motivation to
learn new skills, and excellent verbal and written communication skills are
desirable.
How to apply:
Project 4 applicants should upload a cover letter, CV, and motivation letter outlining why
you want to pursue a PhD to this link (https://forms.gle/ZTjUWotqvodkr9nK7)
before 31/05/2026.
Informal
enquiries to:
Funding:
Annual stipend of €25,000 plus fees for 4
years.
Project 3: PAT Applications for
Monitoring AAV Production
Supervisors:
Dr Jonathan Bones
This project aims to develop
process analytical technologies (PAT) for monitoring AAV production during cell
culture. PAT is widely used for monitoring chemical synthesis and has gained
traction for monitoring manufacturing processes of biopharmaceuticals such as
recombinant proteins and monoclonal antibodies. PAT for AAV remains a challenge
due to the size and complexity of AAV and their lower expression rates when
compared to more standard recombinant proteins.
Here, we aim to explore a
variety of analytical methods, inline, online and atline, facilitated by
automated sampling, as potential PAT approaches for monitoring AAV production
in small scale bioreactors. As part of the project, you will run these reactors
to generate AAV and combine this with the deployment of various spectroscopic
methods or other integrated analytical techniques. As these measurements are
expected to generate considerable volumes of data, you will also develop
strategies for the management and analysis of the data using various
statistical approaches with a view to understanding how we can ultimately use
PAT for advanced process control.
This exciting project offers a
mix of molecular biology, cell culture, automation, advanced analytics and data
analytics. We are looking for candidates that are interested in these areas and
who have a desire to better understand how processes work and to use their
combined skills to push for improvement in process performance.
Candidate profile: Applicants should hold or expect to receive an upper 2.1 or 1.1
degree in a relevant discipline such as analytical science, analytical
chemistry, bioanalytical science, biotechnology or chemical engineering.
Experience with statistical analysis, particularly multivariate statistics and
data modelling would be an advantage. Training will be provided in additional
aspects of biology required for successful completion of the programme. The
ability to work as part of a team, an interest in industrially focused
research, motivation to learn new skills as well as excellent written and oral
skills is also desirable.
How to apply:
For Project 3 applicants should email a covering letter,
a motivation statement as well as outlining why you would like to do a PhD to careers@nibrt.ie.
You
will also need to forward a copy of your CV along with your academic
referees.
Informal enquiries to:
Funding:
Annual stipend of €25,000 plus fees for 4
years.
Transformation of Advanced
Medicines Manufacture (TRANS-AM)
Gene
therapies are a type of advanced medicine that represent exciting possibilities
to treat and potentially cure many life-altering and life-threatening diseases.
They also represent a huge growth area with several hundred currently in
various stages of development. Many of these are based on using recombinant
Adeno-associated virus (rAAV) as a delivery vector. If even a small portion of
them reach the market, current manufacturing and characterisation technologies
in the industry will struggle to deliver them economically and safely for
patients.
This
research program aims to provide innovative solutions to help overcome the
manufacturing challenges associated with producing rAAV and brings together
experts from two leading Irish institutions, NIBRT and UCD, and APC-VLE Ltd. (https://approcess.com/services/cell-and-gene-therapies)
- a leading Irish industrial partner - in an exciting 5-year collaborative
program.
We
are currently seeking applicants for three PhD projects as listed below. The
successful candidates will be based in either NIBRT or UCD and will also spend
some time on placements in the industrial partner.
We are seeking
ambitious, inquisitive and innovative individuals to join our multidisciplinary
research team. As part of a dynamic and collaborative environment, you will
contribute to breakthrough work that supports the scalable, efficient, and
high-quality production of viral vectors—laying the foundation for
next-generation treatments for genetic diseases. If you're excited by the
intersection of biotechnology, process development, and therapeutic innovation,
we’d love to hear from you.
The National Institute for Bioprocessing Research and
Training (‘NIBRT’) is a global centre of excellence, headquartered in
Dublin that provides training and research solutions to the global
biopharmaceutical manufacturing sector. NIBRT arose from an innovative
collaboration between University College Dublin, Trinity College Dublin, Dublin
City University and the Institute of Technology, Sligo, with core funding from
the Government of Ireland through Ireland’s inward investment agency, IDA
Ireland. NIBRT’s 8,300 m² facility has over 100 employees currently and houses
fully operational pilot plants for biologics manufacturing training to industry
and education, multiple research laboratories focused on biopharmaceuticals
manufacturing research and a dedicated facility focused on the early-stage
development of biologics and advanced therapy products. The facilities and
infrastructure are world-leading and provide a vibrant environment for delivery
of excellent science and translation research and opportunities for career
growth, development and progression.
UNIVERSITY COLLEGE
DUBLIN (UCD) is one of Europe’s leading
research-intensive universities where undergraduate education, postgraduate
masters and PhD training, research, innovation and community engagement form a
dynamic continuum of activity. The University was established in 1854 by John
Henry Newman whose classic work The Idea of a University is one of the most
enduring texts on the value of higher education and a source of inspiration for
UCD’s current educational philosophy.
Today UCD
is Ireland’s largest university with almost 25,000 students. It is the most
popular destination for Irish school-leavers and actively promotes university
life as a journey of academic and personal discovery through its highly
innovative and flexible UCD Horizons undergraduate curriculum. UCD is Ireland’s
leader in postgraduate education with almost 7,000 postgraduate students,
representing approximately 28% of the UCD student population, and almost 2,000
PhD students. Over 50% of UCD undergraduates progress to postgraduate studies.
Project 1: CRISPR library screening
to identify endogenous HEK293 genes that impact AAV production
Supervisors:
Prof. Niall Barron & Assoc. Prof. Colin Clarke
About the project:
A strategy that has proven very successful
in identifying the genetic basis of various
cellular phenotypes, including diseases
such as cancer, cellular behaviour in bioreactors and identifying viral
restriction factors, is the use of CRISPR library screens. These can be either
to knockout the genes expressed in a cell or to activate the expression of
silent genes. The advantage is that it is relatively unbiased and has the
potential to target every gene in the genome.
Aims and Objectives: In this project we will use this strategy in order to screen a
suspension-adapted HEK293 cell line for genes that contribute to or inhibit the
production of AAV gene therapy vectors. We will use a human CRISPR/guide RNA
library to create a HEK293 cell population within which every gene has been
targeted for deletion. We will select a sub-population
of cells with the highest and lowest level of AAV production and this
population of cells will be sequenced to identify which guide RNAs are
enriched, thereby identifying their target genes. The most impactful genes will
be validated by knocking out in parental HEK293 cells and then testing AAV
production yield after triple transfection.
Candidate profile: Applicants should hold or expect to receive an upper 2.1 or 1.1
degree in a relevant discipline. A cell biology/molecular biology background would
be ideal. Training will be provided in advanced methods and approaches in cell
and molecular biology required for successful completion of the programme. The
ability to work as part of a team, a strong interest in applied research,
motivation to learn new skills as well as excellent written and oral skills are
essential.
Example publications from the Lab:
·
Production of an Oncolytic
Adeno-Associated Virus Containing the Pro-Apoptotic TRAIL Gene Can Be Improved
by shRNA Interference. 2025 Int J Mol Sci. Link
·
Multiplex genome editing eliminates
lactate production without impacting growth rate in mammalian cells. 2025 Nat
Metab. Link
·
Detection of host cell
microprotein impurities in antibody drug products. 2024 Nature
Communications. Link
· A Direct Comparison of rAAV5 Variants Derived from the Baculovirus
Expression System Using LC-MS Workflows Demonstrates Key Differences in Overall
Production Yield, Product Quality and Vector Efficiency. 2024 Int J Mol Sci.
Link
How to apply:
Project 1 applicants should email: a cover
letter
(including your motivation statement outlining why you wish to do a PhD and why you are suited to this project), a CV,
and contact details for your academic
referees to careers@nibrt.ie.
Informal enquiries to:
Funding:
Annual stipend of €25,000 plus fees for 4
years.
Project 2: Improving rAAV safety
through glycoengineering
Supervisors: Dr Ioscani Jiménez del Val
Recombinant
adeno-associated viruses (rAAVs) are the leading vectors for gene therapy, with
eight rAAV-based therapies with regulatory approval (EMA and/or FDA) and over
250 rAAV-based therapies undergoing clinical trials. Despite their success in
treating life-threatening illnesses, the rAAV doses required to achieve
therapeutic benefit often lead to immune responses that reduce efficacy and, in
extreme cases, may lead to patient death.
The capsid proteins
of rAAVs are decorated with complex carbohydrates (glycans), the composition of
which may drive dangerous immune responses in patients. For example, the immune
system is known to target high mannose carbohydrates present on the envelope of
several pathogenic viruses. Recent research has found that the majority of rAAV
glycans are high-mannose, further suggesting that glycans play an important
role in rAAV safety.
This project aims to
engineer rAAV carbohydrates, converting pathogenic high-mannose structures into
non-immunogenic forms. Initially, the project will remodel rAAV glycans using
in vitro methods. Once the immunological benefit of rAAV glycoengineering is
established, the project will continue with genetically engineering HEK293
cells, the most widely used host for rAAV production, to yield gene therapy
vectors with non-immunogenic glycans.
This exciting project
offers a mix of enzyme catalysis, molecular biology, cell culture, in vitro
assay development, and data analytics. We are looking for candidates that are
interested in these areas and who wish to deploy genetic engineering strategies
to advance the safety and efficacy of next-generation biological medicines.
Candidate profile: Applicants should hold or expect to receive an upper 2.1 or 1.1
degree in a relevant discipline, such as Biochemistry, Biotechnology, Cell
Biology, or Biochemical Engineering. Experience in mammalian cell culture and
molecular biology techniques are preferred. Training will be provided on the
methods required for successful project completion. Teamwork, motivation to
learn new skills, and excellent verbal and written communication skills are
desirable.
How to apply:
Project 4 applicants should upload a cover letter, CV, and motivation letter outlining why
you want to pursue a PhD to this link (https://forms.gle/ZTjUWotqvodkr9nK7)
before 31/05/2026.
Informal
enquiries to:
Funding:
Annual stipend of €25,000 plus fees for 4
years.
Project 3: PAT Applications for
Monitoring AAV Production
Supervisors:
Dr Jonathan Bones
This project aims to develop
process analytical technologies (PAT) for monitoring AAV production during cell
culture. PAT is widely used for monitoring chemical synthesis and has gained
traction for monitoring manufacturing processes of biopharmaceuticals such as
recombinant proteins and monoclonal antibodies. PAT for AAV remains a challenge
due to the size and complexity of AAV and their lower expression rates when
compared to more standard recombinant proteins.
Here, we aim to explore a
variety of analytical methods, inline, online and atline, facilitated by
automated sampling, as potential PAT approaches for monitoring AAV production
in small scale bioreactors. As part of the project, you will run these reactors
to generate AAV and combine this with the deployment of various spectroscopic
methods or other integrated analytical techniques. As these measurements are
expected to generate considerable volumes of data, you will also develop
strategies for the management and analysis of the data using various
statistical approaches with a view to understanding how we can ultimately use
PAT for advanced process control.
This exciting project offers a
mix of molecular biology, cell culture, automation, advanced analytics and data
analytics. We are looking for candidates that are interested in these areas and
who have a desire to better understand how processes work and to use their
combined skills to push for improvement in process performance.
Candidate profile: Applicants should hold or expect to receive an upper 2.1 or 1.1
degree in a relevant discipline such as analytical science, analytical
chemistry, bioanalytical science, biotechnology or chemical engineering.
Experience with statistical analysis, particularly multivariate statistics and
data modelling would be an advantage. Training will be provided in additional
aspects of biology required for successful completion of the programme. The
ability to work as part of a team, an interest in industrially focused
research, motivation to learn new skills as well as excellent written and oral
skills is also desirable.
How to apply:
For Project 3 applicants should email a covering letter,
a motivation statement as well as outlining why you would like to do a PhD to careers@nibrt.ie.
You
will also need to forward a copy of your CV along with your academic
referees.
Informal enquiries to:
Funding:
Annual stipend of €25,000 plus fees for 4
years.
